tbuckley/cabot-search huggingface dataset:
Associations of Cardiometabolic Multimorbidity With All-Cause and Coronary Heart Disease Mortality Among Black Adults in the Jackson Heart Study
Authors: Joshua J. Joseph, Aakash Rajwani, Daniel Roper, Songzhu Zhao, David Kline, James Odei, Guy Brock, Justin B. Echouffo-Tcheugui, Rita R. Kalyani, Alain G. Bertoni, Valery S. Effoe, Mario Sims, Wen-Chi Wu, Gary S. Wand, Sherita H. Golden
Journal: JAMA Network Open (2022)

Importance A combination of diabetes, coronary heart disease (CHD), and stroke has multiplicative all-cause mortality risk compared with any individual morbidity in White populations, but there is a lack of studies in Black populations in the US. Objective To examine the association of cardiometabolic multimorbidity (diabetes, stroke, and CHD) individually and collectively with all-cause and CHD mortality. Design, Setting, and Participants This cohort study included Black adults in the Jackson Heart Study followed over a median of 15 years. Baseline examinations were performed between 2000 and 2004, with follow-up on all-cause and CHD mortality through May 31, 2018. Participants were categorized into mutually exclusive groups at baseline: (1) free of cardiometabolic morbidity, (2) diabetes, (3) CHD, (4) stroke, (5) diabetes and stroke, (6) CHD and stroke, (7) diabetes and CHD, and (8) diabetes, stroke, and CHD. Data were analyzed from 2019 to 2021. Exposure Cardiometabolic disease alone or in combination. Main Outcomes and Measures The main outcomes were all-cause mortality and CHD mortality. Cox models estimated hazard ratios (HRs) with 95% CIs adjusted for sociodemographic and cardiovascular risk factors. Results Among 5064 participants (mean [SD] age, 55.4 [12.8] years; 3200 [63%] women) in the Jackson Heart Study, 897 (18%) had diabetes, 192 (4%) had CHD, and 104 (2%) had a history of stroke. Among participants with cardiometabolic morbidities, the crude all-cause mortality rates were lowest for diabetes alone (24.4 deaths per 1000 person-years) and highest for diabetes, CHD, and stroke combined (84.1 deaths per 1000 person-years). For people with only 1 cardiometabolic morbidity, risk for all-cause mortality was highest for people with stroke (HR, 1.74; 95% CI, 1.24-2.42), followed by CHD (HR, 1.59 (95% CI, 1.22-2.08) and diabetes (HR, 1.50; 95% CI, 1.22-1.85), compared with no cardiometabolic morbidities. There were also increased risks of mortality with combinations of diabetes and stroke (HR, 1.71; 95% CI, 1.09-2.68), CHD and stroke (HR, 2.23; 95% CI, 1.35-3.69), and diabetes and CHD (HR, 2.28; 95% CI, 1.65-3.15). The combination of diabetes, stroke, and CHD was associated with the highest all-cause mortality (HR, 3.68; 95% CI, 1.96-6.93). Findings were similar for CHD mortality, but with a larger magnitude of association (eg, diabetes, stroke, and CHD: HR, 13.52; 95% CI, 3.38-54.12). Conclusions and Relevance In this cohort study, an increasing number of cardiometabolic multimorbidities was associated with a multiplicative increase in risk of all-cause mortality among Black adults, with a greater magnitude of association for CHD mortality.
Association Between In-Person vs Telehealth Follow-up and Rates of Repeated Hospital Visits Among Patients Seen in the Emergency Department
Authors: Vivek V. Shah, Chad W. Villaflores, Linh H. Chuong, Richard K. Leuchter, Austin S. Kilaru, Sitaram Vangala, Catherine A. Sarkisian
Journal: JAMA Network Open (2022)

Importance For patients discharged from the emergency department (ED), timely outpatient in-person follow-up is associated with improved mortality, but the effectiveness of telehealth as follow-up modality is unknown. Objective To evaluate whether the rates of ED return visits and hospitalization differ between patients who obtain in-person vs telehealth encounters for post-ED follow-up care. Design, Setting, and Participants This retrospective cohort study included adult patients who presented to either of 2 in-system EDs of a single integrated urban academic health system from April 1, 2020, to September 30, 2021; were discharged home; and obtained a follow-up appointment with a primary care physician within 14 days of their index ED visit (15 total days). Exposures In-person vs telehealth post–ED discharge follow-up within 14 days. Main Outcomes and Measures Multivariable logistic regression was used to estimate the odds of ED return visits (primary outcome) or hospitalization (secondary outcome) within 30 days of an ED visit based on the modality of post–ED discharge follow-up. Models were adjusted for age, sex, primary language, race, ethnicity, Social Vulnerability Index, insurance type, distance to the ED, ambulatory billing codes for the index visit, and the time from ED discharge to follow-up. Results Overall, 12 848 patients with 16 987 ED encounters (mean [SD] age, 53 [20] years; 9714 [57%] women; 2009 [12%] Black or African American; 3806 [22%] Hispanic or Latinx; and 9858 [58%] White) were included; 11 818 (70%) obtained in-person follow-up, and 5169 (30%) obtained telehealth follow-up. Overall, 2802 initial ED encounters (17%) led to returns to the ED, and 676 (4%) led to subsequent hospitalization. In adjusted analyses, telehealth vs in-person follow-up visits were associated with increased rates of ED returns (28.3 [95% CI, 11.3-45.3] more ED returns per 1000 encounters) and hospitalizations (10.6 [95% CI, 2.9-18.3] more hospitalizations per 1000 encounters). Conclusions and Relevance In this cohort study of patients in an urban integrated health care system, those with telehealth follow-up visits after an ED encounter were more likely to return to the ED and be hospitalized than patients with in-person follow-up. The use of telehealth warrants further evaluation to examine its effectiveness as a modality for continuing care after an initial ED presentation for acute illness.
MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation for Patients With Persistent Atrial Fibrillation
Authors: Luuk H. G. A. Hopman, Pranav Bhagirath, Marco J. W. Götte
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples
Authors: Haitao Zhao, Sijun Pan, Auginia Natalia, Xingjie Wu, Chin-Ann J. Ong, Melissa C. C. Teo, Jimmy B. Y. So, Huilin Shao
Journal: Nature Biomedical Engineering (2022)
Mitochondrial dysfunction reactivates α-fetoprotein expression that drives copper-dependent immunosuppression in mitochondrial disease models
Authors: Kimberly A. Jett, Zakery N. Baker, Amzad Hossain, Aren Boulet, Paul A. Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John DeCoteau, Karen Mochoruk, George N. Ioannou, Christopher Savard, Sai Yuan, Osama H.M.H. Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J. Battersby, Vishal M. Gohil, Scot C. Leary
Journal: Journal of Clinical Investigation (2022)

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative phosphorylation. Collectively, our data argue that α-fetoprotein may be secreted by bioenergetically stressed tissue to suppress the immune system, an effect that may explain the recurrent or chronic infections that are observed in a subset of mitochondrial diseases or in other disorders with secondary mitochondrial dysfunction.
Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity
Authors: Christian Meyer zu Natrup, Alina Tscherne, Christine Dahlke, Malgorzata Ciurkiewicz, Dai-Lun Shin, Anahita Fathi, Cornelius Rohde, Georgia Kalodimou, Sandro Halwe, Leonard Limpinsel, Jan H. Schwarz, Martha Klug, Meral Esen, Nicole Schneiderhan-Marra, Alex Dulovic, Alexandra Kupke, Katrin Brosinski, Sabrina Clever, Lisa-Marie Schünemann, Georg Beythien, Federico Armando, Leonie Mayer, Marie L. Weskamm, Sylvia Jany, Astrid Freudenstein, Tamara Tuchel, Wolfgang Baumgärtner, Peter Kremsner, Rolf Fendel, Marylyn M. Addo, Stephan Becker, Gerd Sutter, Asisa Volz
Journal: Journal of Clinical Investigation (2022)

The SARS-CoV-2 spike (S) glycoprotein is synthesized as a large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as a candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S-infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/S2 cleavage site and K986P and V987P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of broadly reactive anti-S antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.
Anti-CTLA-4 antibodies drive myeloid activation and reprogram the tumor microenvironment through FcγR engagement and type I interferon signaling
Authors: Ido Yofe, Tomer Landsberger, Adam Yalin, Isabelle Solomon, Cristobal Costoya, Dafne Franz Demane, Mansi Shah, Eyal David, Chamutal Borenstein, Oren Barboy, Ignacio Matos, Karl S. Peggs, Sergio A. Quezada, Ido Amit
Journal: Nature Cancer (2022)
Retrospectively modeling the effects of increased global vaccine sharing on the COVID-19 pandemic
Authors: Sam Moore, Edward M. Hill, Louise Dyson, Michael J. Tildesley, Matt J. Keeling
Journal: Nature Medicine (2022)

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused considerable morbidity and mortality worldwide. The protection provided by vaccines and booster doses offered a method of mitigating severe clinical outcomes and mortality. However, by the end of 2021, the global distribution of vaccines was highly heterogeneous, with some countries gaining over 90% coverage in adults, whereas others reached less than 2%. In this study, we used an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries in 2021, to investigate the global impact of different potential vaccine sharing protocols that attempted to address this inequity. We quantified the effects of implemented vaccine rollout strategies on the spread of SARS-CoV-2, the subsequent global burden of disease and the emergence of novel variants. We found that greater vaccine sharing would have lowered the total global burden of disease, and any associated increases in infections in previously vaccine-rich countries could have been mitigated by reduced relaxation of non-pharmaceutical interventions. Our results reinforce the health message, pertinent to future pandemics, that vaccine distribution proportional to wealth, rather than to need, may be detrimental to all.
Commentary
Authors: Marco Spadaccini, Klaus Mönkemüller
Journal: Endoscopy (2022)

Artificial intelligence (AI) is assumed to improve the detection of colorectal lesions, thus helping to reduce the risk of interval cancer after screening colonoscopy [1] [2] [3]. However, endoscopists need to be aware that AI systems should be used to assist and not to replace them. As a matter of concrete experience, this video underlines the crucial role of the endoscopist, who is ultimately in charge and responsible for detecting lesions underrepresented in AI training datasets (i. e., flat lesions such as sessile serrated lesions, and nongranular laterally spreading lesions) by performing a thorough and methodical inspection, using both proper mucosal exposure and applying human visual detection skills. In the future, the capability of AI systems to detect flat and subtle lesions will likely be improved, hopefully minimizing the risk of missing important premalignant lesions; however, we do not envisage a day when the role of the endoscopist becomes negligible.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: EUS-guided radiofrequency ablation of pancreatic/peripancreatic tumors and oligometastatic disease: an observational prospective multicenter studyEndosc Int Open 2022; 10(10): E1380-E1385DOI: 10.1055/a-1922-4536 Comment on: Assigning a different endoscopist for each annual follow-up may contribute to improved gastric cancer detection ratesEndosc Int Open 2022; 10(10): E1333-E1342DOI: 10.1055/a-1922-6429 Comment on: Premedication with simethicone for improving the quality of gastric mucosal visualization: a double-blind randomized controlled trialEndosc Int Open 2022; 10(10): E1343-E1349DOI: 10.1055/a-1922-7773
Clinical phenotypes and long-term outcome of kidney involvement in Erdheim-Chester histiocytosis
Authors: Thibaud Chazal, Francesco Pegoraro, Gaia Manari, Alessandra Bettiol, Valerio Maniscalco, Elena Gelain, Frédéric Charlotte, Roei D. Mazor, Raphaele Renard-Penna, Zahir Amoura, Fleur Cohen-Aubart, Julien Haroche, Hassan Izzedine, Augusto Vaglio
Journal: Kidney International (2022)
An In Vitro Engineered Osteochondral Model as Tool to Study Osteoarthritis Environment
Authors: Annachiara Scalzone, Giorgia Cerqueni, Xiao‐Nong Wang, Ana Ferreira‐Duarte, Kenny Dalgarno, Monica Mattioli‐Belmonte, Piergiorgio Gentile
Journal: Advanced Healthcare Materials (2022)

Abstract Osteoarthritis (OA) is a joint degenerative pathology characterized by mechanical and inflammatory damages affecting synovium, articular cartilage (AC), and subchondral bone (SB). Several in vitro, in vivo, and ex vivo models are developed to study OA, but to date the identification of specific pharmacological targets seems to be hindered by the lack of models with predictive capabilities. This study reports the development of a biomimetic in vitro model of AC and SB interface. Gellan gum methacrylated and chondroitin sulfate/dopamine hydrogels are used for the AC portion, whereas polylactic acid functionalized with gelatin and nanohydroxyapatite for the SB. The physiological behavior of immortalized stem cells (Y201s) and Y201s differentiated in chondrocytes (Y201‐Cs), respectively, for the SB and AC, is demonstrated over 21 days of culture in vitro in healthy and pathological conditions, whilst modeling the onset of cytokines‐induced OA. The key metrics are: lower glycosaminoglycans production and increased calcification given by a higher Collagen X content, in the AC deep layer; higher expression of pro‐angiogenic factor ( vegf ) and decreased expression of osteogenic markers ( coll1, spp1, runx2 ) in the SB. This novel approach provides a new tool for studying the development and progression of OA.
Graphene Oxide Nanoscale Platform Enhances the Anti‐Cancer Properties of Bortezomib in Glioblastoma Models
Authors: Paul S. Sharp, Maria Stylianou, Luis M. Arellano, Juliana C. Neves, Alfredo M. Gravagnuolo, Abbie Dodd, Katharine Barr, Neus Lozano, Thomas Kisby, Kostas Kostarelos
Journal: Advanced Healthcare Materials (2022)

Graphene-based 2D nanomaterials possess unique physicochemical characteristics which can be utilized in various biomedical applications, including the transport and presentation of chemotherapeutic agents. In glioblastoma multiforme (GBM), intratumorally administered thin graphene oxide (GO) nanosheets demonstrate a widespread distribution throughout the tumor volume without impact on tumor growth, nor spread into normal brain tissue. Such intratumoral localization and distribution can offer multiple opportunities for treatment and modulation of the GBM microenvironment. Here, the kinetics of GO nanosheet distribution in orthotopic GBM mouse models is described and a novel nano-chemotherapeutic approach utilizing thin GO sheets as platforms to non-covalently complex a proteasome inhibitor, bortezomib (BTZ), is rationally designed. Through the characterization of the GO:BTZ complexes, a high loading capacity of the small molecule on the GO surface with sustained BTZ biological activity in vitro is demonstrated. In vivo, a single low-volume intratumoral administration of GO:BTZ complex shows an enhanced cytotoxic effect compared to free drug in two orthotopic GBM mouse models. This study provides evidence of the potential that thin and small GO sheets hold as flat nanoscale platforms for GBM treatment by increasing the bioavailable drug concentration locally, leading to an enhanced therapeutic effect.
Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters
Authors: Seong-Ki Lee, Rossana Occhipinti, Fraser J. Moss, Mark D. Parker, Irina I. Grichtchenko, Walter F. Boron
Journal: Journal of the American Society of Nephrology (2022)

Differentiating among HCO 3- , CO 3= , and H + movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO 3- (mechanism 1), the inward flux of 1 CO 3= (mechanism 2), and the CO 2 /HCO 3- -stimulated outward flux of 2 H + (mechanism 3).
Integrating Community Health Workers Into Care for Patients With Advanced Stages of Cancer—Fragility Index Analysis
Authors: James H. B. Im, Ronald Chow, Elizabeth Horn Prsic
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Clonal expansion and epigenetic inheritance of long-lasting NK cell memory
Authors: Timo Rückert, Caleb A. Lareau, Mir-Farzin Mashreghi, Leif S. Ludwig, Chiara Romagnani
Journal: Nature Immunology (2022)

Clonal expansion of cells with somatically diversified receptors and their long-term maintenance as memory cells is a hallmark of adaptive immunity. Here, we studied pathogen-specific adaptation within the innate immune system, tracking natural killer (NK) cell memory to human cytomegalovirus (HCMV) infection. Leveraging single-cell multiomic maps of ex vivo NK cells and somatic mitochondrial DNA mutations as endogenous barcodes, we reveal substantial clonal expansion of adaptive NK cells in HCMV
<i>Yap1</i> modulates cardiomyocyte hypertrophy via impaired mitochondrial biogenesis in response to chronic mechanical stress overload
Authors: Peng Yue, Yue Zhang, Lei Liu, Kaiyu Zhou, Shutao Xia, Mou Peng, Hualin Yan, Xiaoqiang Tang, Zhan Chen, Donghui Zhang, Junling Guo, William T. Pu, Yuxuan Guo, Yimin Hua, Yifei Li
Journal: Theranostics (2022)

Rationale: Chronic pressure overload is a major trigger of cardiac pathological hypertrophy that eventually leads to heart disease and heart failure.Understanding the mechanisms governing hypertrophy is the key to develop therapeutic strategies for heart diseases.Methods: We built chronic pressure overload mice model by abdominal aortic constriction (AAC) to explore the features of Yes-associated protein 1 (YAP1).Then AAV-cTNT-Cre was applied to Yap1 F/F mice to induce mosaic depletion of YAP1.Myh6 CreERT2 ; H11 CAG-LSL-YAP1 mice were involved to establish YAP1 overexpression model by Tomaxifen injection.ATAC-seq and bioChIP-seq were used to explore the potential targets of YAP1, which were verified by a series of luciferase reporter assays.Dnm1l and Mfn1 were re-expressed in AAC mice by AAV-cTNT-Dnm1l and AAV-cTNT-Mfn1.Finally, Verteprofin was used to inhibit YAP1 to rescue cardiac hypertrophy.Results: We found that pathological hypertrophy was accompanied with the activation of YAP1.Cardiomyocyte-specific deletion of Yap1 attenuated AAC-induced hypertrophy.Overexpression of YAP1 was sufficient to phenocopy AAC-induced hypertrophy.YAP1 activation resulted in the perturbation of mitochondria ultrastructure and function, which was associated with the repression of mitochondria dynamics regulators Dnm1l and Mfn1.Mitochondrial-related genes Dnm1l and Mfn1, are significantly targeted by TEAD1/YAP complex.Overexpression of Dnm1l and Mfn1 synergistically rescued YAP1-induced mitochondrial damages and cardiac hypertrophy.Pharmacological repression of YAP1 by verteporfin attenuated mitochondrial damages and pathological hypertrophy in AAC-treated mice.Interestingly, YAP1-induced mitochondria damages also led to increased reactive oxidative species, DNA damages, and the suppression of cardiomyocyte proliferation.Conclusion: Together, these data uncovered YAP signaling as a therapeutic target for pressure overload-induced heart diseases and cautioned the efforts to induce cardiomyocyte regeneration by activating YAP.